Uncontrolled inflammation in the small airways remains a major unmet need in clinical pulmonology. Severely asthmatic patients suffer from life-threatening symptoms and often have exacerbations requiring costly emergency hospital treatments. Although asthma patients are prescribed large numbers of inhalers, these current devices deliver very little medication into the lungs, often less than 1% into small airways, which remain untreated. Therefore, we are developing a new method of delivering medication to the small airways which will perform significantly better than current devices. We will create a novel highly dispersible dry powder formulation containing budesonide, a well-studied corticosteroid medication and a hygroscopic excipient (inactive ingredient) resulting in an excipient enhanced growth (EEG) formulation. This EEG formulation will be able to uniquely treat inflammation in small airways in order to significantly reduce related symptoms of severe asthma. By creating extra-fine sized (submicrometer) drug powder particles combined with a hygroscopic excipient, the particles are able to avoid depositing in the mouth and throat and then will grow hygroscopically during inhalation to an optimal size to target the small airways with high deposition. The powder formulation will be delivered by a high efficiency dry powder inhaler including a novel 3D rod array structure that was demonstrated to best deaggregate carrier-free powder formulations. These new formulation and inhaler combinations have been shown to achieve emitted doses greater than 75%, fine particle fractions (<5 m in size) of greater than 90% and initial mass median aerodynamic diameters (MMAD) less than 1.5 m, which result in mouth-throat depositional losses of less than 5%. The high efficiency drug delivery will increase drug deposition in untreated lung regions and reduce systemic drug exposure compared to current devices. We will select and evaluate two powder formulation candidates by testing their chemical stability, physico-chemical characteristics, and aerosol performance in a realistic airway in-vitro model in order to maximize the effectiveness of the formulation. This application is the first step in a translational plan to commercialize the excipient enhanced growth concept developed in the labs of Drs. Hindle and Longest at Virginia Commonwealth University, supported by R01 and R21 grants from the National Heart, Lung, and Blood Institute (NHLBI), which has produced over 30 publications and two granted patents. The translation of this technology into a clinically beneficial product will revolutionize drug delivery and symptom control by delivering medicine to currently untreated regions of the airways.